title: HypoxamiRs and cancer: from biology to targeted therapy.
abstract: CONCLUSIONS
  Hypoxia is a hallmark of the tumor microenvironment and represents a major source of failure in cancer therapy.
  
  
  BACKGROUND
  Recent work has generated extensive evidence that microRNAs (miRNAs) are significant components of the adaptive response to low oxygen in tumors. Induction of specific miRNAs, collectively termed hypoxamiRs, has become an accepted feature of the hypoxic response in normal and transformed cells.
  
  
  RESULTS
  Overexpression of miR-210, the prototypical hypoxamiR, is detected in most solid tumors, and it has been linked to adverse prognosis in many tumor types. Several miR-210 target genes, including iron-sulfur (Fe-S) cluster scaffold protein (ISCU) and glycerol-3-phosphate dehydrogenase 1-like (GPD1L), have been correlated with prognosis in an inverse fashion to miR-210, suggesting that their down- regulation by miR-210 occurs in vivo and contributes to tumor growth. Additional miRNAs are modulated by decreased oxygen tension in a more tissue-specific fashion, adding another level of complexity over the classic hypoxia-regulated gene network.
  
  
  CONCLUSIONS
  From a biological standpoint, hypoxamiRs are emerging modifiers of cancer cell response to the adaptive challenges of the microenvironment. From a clinical perspective, assessing the status of these miRNAs may contribute to a detailed understanding of hypoxia-induced mechanisms of resistance and/or to the fine-tuning of future hypoxia-modifying therapies.
authors.affiliation: 1 Department of Radiation Oncology, Sydney Cancer Centre, Royal Prince Alfred Hospital , Camperdown, Australia .
authors.forename: Harriet E
authors.initials: HE
authors.lastname: Gee
authors.forename: Cristina
authors.initials: C
authors.lastname: Ivan
authors.forename: George A
authors.initials: GA
authors.lastname: Calin
authors.forename: Mircea
authors.initials: M
authors.lastname: Ivan
mesh_terms: D000818:Animals; D017209:Apoptosis; D015687:Cell Hypoxia; D004249:DNA Damage; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D035683:MicroRNAs / Q000502:physiology*; D008928:Mitochondria / Q000378:metabolism; D058990:Molecular Targeted Therapy; D009369:Neoplasms / Q000098:blood supply / Q000378:metabolism / Q000473:pathology; D059016:Tumor Microenvironment
chemical_list: C543800:MIRN210 microRNA, human; D035683:MicroRNAs